Genetic Variant NM_003059.3:c.498-121A>G (chr5-132313493-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003059.3(SLC22A4):c.498-121A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 875,446 control chromosomes in the GnomAD database, including 195,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 36432 hom., cov: 33)

Exomes 𝑓: 0.66 ( 159242 hom. )

Consequence

SLC22A4
NM_003059.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0980

Publications

19 publications found

Variant links:

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

SLC22A4 links:

MIR3936HG (HGNC:40538): (MIR3936 host gene)

MIR3936HG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-132313493-A-G is Benign according to our data. Variant chr5-132313493-A-G is described in ClinVar as [Benign]. Clinvar id is 1220625.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3 link	c.498-121A>G		intron_variant	Intron 2 of 9	ENST00000200652.4	NP_003050.2	Q9H015

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC22A4	ENST00000200652.4 link	c.498-121A>G	intron_variant	Intron 2 of 9	1	NM_003059.3	ENSP00000200652.3	Q9H015
MIR3936HG	ENST00000621103.4 link	n.825-1240T>C	intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000491257.1 link	n.302-121A>G	intron_variant	Intron 2 of 3	4
MIR3936HG	ENST00000669845.1 link	n.451-1240T>C	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.688

AC:

104597

AN:

151974

Hom.:

36401

Cov.:

show subpopulations

Gnomad AFR

AF:

0.763

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.699

Gnomad EAS

AF:

0.621

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.580

Gnomad NFE

AF:

0.680

Gnomad OTH

AF:

0.693

GnomAD4 exome

AF:

0.658

AC:

475814

AN:

723354

Hom.:

159242

AF XY:

0.646

AC XY:

250412

AN XY:

387366

show subpopulations

African (AFR)

AF:

0.760

AC:

14736

AN:

19384

American (AMR)

AF:

0.713

AC:

31140

AN:

43648

Ashkenazi Jewish (ASJ)

AF:

0.714

AC:

15184

AN:

21252

East Asian (EAS)

AF:

0.636

AC:

23168

AN:

36414

South Asian (SAS)

AF:

0.439

AC:

30911

AN:

70480

European-Finnish (FIN)

AF:

0.567

AC:

28390

AN:

50058

Middle Eastern (MID)

AF:

0.604

AC:

1849

AN:

3062

European-Non Finnish (NFE)

AF:

0.692

AC:

306381

AN:

442924

Other (OTH)

AF:

0.666

AC:

24055

AN:

36132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9162

18323

27485

36646

45808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.688

AC:

104682

AN:

152092

Hom.:

36432

Cov.:

AF XY:

0.677

AC XY:

50335

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.763

AC:

31646

AN:

41498

American (AMR)

AF:

0.702

AC:

10722

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.699

AC:

2426

AN:

3470

East Asian (EAS)

AF:

0.620

AC:

3201

AN:

5164

South Asian (SAS)

AF:

0.437

AC:

2105

AN:

4820

European-Finnish (FIN)

AF:

0.561

AC:

5939

AN:

10578

Middle Eastern (MID)

AF:

0.599

AC:

175

AN:

292

European-Non Finnish (NFE)

AF:

0.680

AC:

46215

AN:

67972

Other (OTH)

AF:

0.693

AC:

1460

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1692

3385

5077

6770

8462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.688

Hom.:

44387

Bravo

AF:

0.709

Asia WGS

AF:

0.524

AC:

1825

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

3.5

(source)

DANN

Benign

0.74

PhyloP100

-0.098

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_003059.3:c.498-121A>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over